1.1 Overview Precision medicine seeks to capitalize on growing capabilities in the areas of genomics, clinical phenotyping, clinical informatics, electronic health record (EHR) availability and interoperability, and mobile health technologies to improve understanding of human health and disease. Improved understanding of the complex interplay of genetic and environmental exposures, beyond those previously available in long-term observational epidemiological research, holds the promise of better prediction, prevention, and treatment of a host of human diseases including coronary heart disease, stroke, numerous cancers, dementing illnesses, arthritis, and other major causes of disability and early death. Internationally, efforts to address the opportunities of precision medicine have led to the assembly of large cohorts in the UK (UK Biobank), the China Kadoorie Biobank, and in a selected sub-population in the US (the Million Veteran Project - MVP). In January 2015, President Obama announced a plan for the Precision Medicine Initiative (PMI) to address this significant scientific opportunity. This is a unified multi-PI application (Drs. Greenland, Ahsan, Daviglus and Winn) from the Illinois Precision Medicine Consortium (IPMC) representing 3 major Chicago-area academic institutions (Northwestern University, University of Chicago, and the University of Illinois at Chicago) and their healthcare provider organization (HPO) partners, in response to OT-PM-18-001, Limited Competition: All of Us Research Program Regional Medical Center Healthcare Provider Organizations (OT2). Our goal is to continue our partnership with the All of Us Research Program (AoURP), to recruit and enroll a diverse patient population, contributing to the overall total of one million or more individuals across all age groups from both sexes, including both healthy people and those with pre-existing diseases (without regard to specific disease type), and to follow them through innovative mobile health technologies, electronic health records (EHR), and health insurance claims data to enable linkage of genetic and environmental exposures with a broad array of health outcomes. This consortium brings together the extensive preexisting research resources across the 3 academic institutions, as well as the widespread, yet geographically distinct, service areas of their HPO partners representing numerous ethnically and socioeconomically diverse Chicago and Illinois communities. These longstanding relationships of trust are well established. The IPMC has so far reached and exceeded milestones for organization, participation in national planning, and successful recruitment and logistics. For the OT award period, we will continue to utilize a highly participatory and empowered model of diverse participant engagement and enrollment. The data collected from the geographically and ethnically diverse IPMC population, representing the largest and most diverse urban metropolitan area in the Midwestern United States, will add significant value to the overall AoURP goal of enrolling, retaining, and interacting with 1 million US residents. We have assembled a multidisciplinary team of academic researchers, community partners, and health system leaders in the past year. This application builds upon the collective experience and demonstrated success of the 3 partnering institutions in assembly and retention of large epidemiological cohorts, questionnaire data collection, community-based participatory research, minority health research, EHR linkage for genetic research, and their established and ongoing cross- institution collaborations. For this 5-year project period, IPMC plans to enroll 20,000 full participants each year during Years 1 to 3, 18,000 full participants in Year 4, and 15,000 full participants in Year 5. As such, we will consent, conduct physical measurements, collect biospecimens, and transmit curated data to the AoURP Data and Research Center (DRC; Vanderbilt University) and processed biosamples to the AoURP Biobank (Mayo Clinic), on at least 93,000 people from diverse ethnic, social, and economic backgrounds. Further, we aim to broaden our enrollment from patients in IPMC HPOs (and their affiliates), to include direct volunteers (DV), once this capability becomes technically feasible. To reach enrollment milestones, we will engage HPO staff, patients, and the general community to generate support for and participation in the HPO cohort. We will also engage DV corporate partners, such as Walgreens which is headquartered in Deerfield, IL, to collaborate on implementation of HPO/DV Hybrid strategies. We will continue detailed tracking of success rates, including percentage participation and diversity of participation, and discern the most effective recruitment strategies for each participating HPO. We will also continuously adapt, refine and introduce new approaches to maintain recruitment targets. When available, we will employ mobile technologies as developed by the Technology Coordinating Center, and continuously engage participants to remain connected to the AoURP. In aggregate, the academic institutions, HPOs, and community partners represented in this application provide unparalleled expertise and opportunity to reach a geographically and demographically broad and diverse population that is representative of the US as a whole. The population of the greater Chicago and Illinois area brings a unique opportunity to study common and unique environmental, behavioral and genetic underpinnings of health and disease that can inform the precision medicine of tomorrow.